Our research mainly concerns the structural and functional relationships among glucagon-related peptides in a variety of tissues. Using several well defined antiglucagon sera we will continue our examination of intestinal and pancreatic glucagon-containing tissues and will expand our studies to other tissues, including those of the nervous system. Using isolated islets of Langerhans as well as other glucagon-producing tissues we will study the biosynthesis of the hormone in order to identify proglucagon and study its conversion to glucagon. We hope to be able to classify various glucagon-containing tissues both with regard to their content of glucagon and glucagon-related forms and with regard to their different mechanisms of post-translational modification of the glucagon precursor. Using a radioimmunoassay which detects the COOH-terminal fragment of glucagon cleaved from larger forms by treatment with trypsin and carboxypeptidase B, we will attempt to isolate and characterize the glucagon precursor. Finally, using methods similar to those described above for glucagon, we will attempt to identify precursors for other small peptide hormones.